TET2 mutations predict response to hypomethylating agents in myelodysplastic syndrome patients
TET2 mutations predict response to hypomethylating agents in myelodysplastic syndrome patients
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DOI：
10.1182/blood-2014-06-582809
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发表时间：
2014-10-23
期刊：
影响因子：
20.3
通讯作者：
Ebert, Benjamin L.
中科院分区：
文献类型：
--
作者：
Bejar, Rafael;Lord, Allegra;Ebert, Benjamin L.
只有少数骨髓增生异常综合征（MDS）患者对低甲基化药物（HMA）有反应，但反应的强预测因子尚不清楚。我们对213例MDS患者在阿扎胞苷（AZA）或地西他滨（DEC）治疗前收集的肿瘤DNA中40个复发突变的髓系恶性肿瘤基因进行了测序。研究突变与缓解和总生存期的关系。47%的总体应答率在药物之间没有差异。当桑格测序（等位基因分数）不太可能检测到亚克隆时，克隆TET 2突变预测了应答（比值比[OR] 1.99，P = .036
Only a minority of myelodysplastic syndrome (MDS) patients respond to hypomethylating agents (HMAs), but strong predictors of response are unknown. We sequenced 40 recurrently mutated myeloid malignancy genes in tumor DNA from 213 MDS patients collected before treatment with azacitidine (AZA) or decitabine (DEC). Mutations were examined for association with response and overall survival. The overall response rate of 47% was not different between agents. Clonal TET2 mutations predicted response (odds ratio [OR] 1.99, P = .036) when subclones unlikely to be detected by Sanger sequencing (allele fraction